The proposal research is based on extensive previous studies of ferritin isomers and their metabolism in normal, developing and malignant cells. It has three main objectives (1) to determine the exact number of genetic cistrons involved in defining the structure of isoferritins of normal, developing and malignant tissues of the rat, by completing detailed studies of the subunit structure and peptide composition of this multimeric protein; (2) to learn to manipulate these changes in gene expression for ferritin by studying the effects of iron and other factors in two kinds of systems: during development of the rat and by in vitro transformation of cells in tissue culture; (3) to explore the possibility that isoferritins and their iron saturation may be used diagnostically as a chemical index of malignancy in the human. BIBLIOGRAPHIC REFERENCES: Linder, M.C., Moor, J.R. and Munro, H.N. Differences in ferritin structure in normal and malignant rat tissues. Bioch. Biophys. Acta 386, 409-421, 1975. Vulimiri, L., Catsimpoolas, N., Griffith, A.L., Linder, M.C. and Munro, H.N. Size and charge heterogeneity of rat tissue ferritins. Bioch. Biophys. Acta 412, 148-156, 1975.